Purdue University researcher, Gary Blau, wrote this on Tuesday:
Pat: I am looking to answers to this question not only for those following a transplant but for us elderly and frail types who jump right to maintenance following consolidation. I hope you will also address the issue of becoming refractory to maintenance agents. Shouldn’t we be saving their use until needed?
How about dosage regimen. It seems to me that in the past you decried the three year maintenance period at UAMS. Have you changed your perspective?
“Elderly and frail types.” Really Gary? You certainly don’t look “frail” in this picture you sent me a while back!
Although most maintenance therapy studies focus on results following one or more stem cell transplants, my understanding is someone using maintenance following consolidation without a stem cell transplant can expect similar results.
I have personal experience with this. I chose to skip undergoing a stem cell transplant after my Rev/dex induction therapy worked so well after I was diagnosis in 2007. Instead, I chose to stay on Rev/dex–eventually we dropped the dex–and see what happened. I was able to achieve CRa short ten months later.
A few years into my maintenance therapy, I started receiving pressure to transplant. So what did I do? I sought a second opinion, of course!
At a face to face consult with the IMF’s Dr. Brian Durie, his assessment and opinion was decisive: “Why would you transplant now?” He asked. “Why change a therapy that’s working?”
But that’s not why I brought-up our meeting. Dr. Durie went-on to explain that a patient who responds well to Revlimid can expect it to work for an average of four years. I’m not sure if Dr. Durie was referencing studies post SCT or not.
But like clockwork, Revlimid stopped working for me exactly four years and one month following my initial exposure.
I read an Italian study a while back which showed that the combination of Velcade and prednisone was an effective maintenance therapy alternative in older patients who did not qualify for a stem cell transplant.
Maybe some of you can jump-in here and highlight some specific examples…
Gary also asked about “the issue of becoming refractory to maintenance agents. Shouldn’t we be saving their use until needed?”
The answer is “maybe.” I addressed this issue yesterday, writing:
...the standard of care these days is to keep relapsed patients on meds continually. The theory is allowing advanced myeloma to gain momentum risks facing the beginning of the end; a runaway freight train that can’t be stopped once therapy is resumed.
Well, apparently Mayo Clinic and University of Minnesota docs don’t necessarily agree! One of the patients I spoke with was on a drug free holiday following his third relapse, despite not having any medical issues that might force him to stay off chemo.
This regional anomaly highlights my theory. Sue (Patient One), stays on maintenance and her myeloma is held-down for an extended period of time. But when it busts-out, it has become resistant to one of the two main drugs that could be used to knock-it-back.
Randy (Patient Two), stops using Revlimid as soon as they achieve a complete response (CR), or their myeloma becomes stable and they achieve a very good partial response (VGPR).
Randy’s myeloma returns a full year earlier than Sue’s. BUT Randy’s myeloma isn’t as drug resistant as Sue’s. So the Revlimid works for Randy, knocking his myeloma back and keeping it stable for 18 months.
In the end, both patients ends-up in the same place!
However, more and more myeloma experts are opting to keep their patients on maintenance therapy indefinitely. I spoke with several last year at ASH. They all felt strongly that ongoing, continual maintenance should be the standard of care, especially for relapsed patients.
Finally, I don’t want to blow-off the last part of Gary’s question:
How about dosage regimen. It seems to me that in the past you decried the three year maintenance period at UAMS. Have you changed your perspective?
Gary, I am changing my perspective. It looks like as many as 50% of low risk Total Therapy 3 patients achieve CR. Many of those are still in remission years later. While it is too soon to tell for sure, trend lines point to median survival rates that will blow-past ten years.
Outspoken Total Therapy supporter, Nick van Dyk, believes the vast majority of these patients to be “cured.” Without debating that point, one would be blind not to notice how different Total Therapy survival curves look as compared to most others.
Have you ever seen a survival line extending-out like that? I don’t care if it is only focused on low risk patients!
If I could, I believe Gary’s criticism of Total Therapy is both the high doses administered and the length of time these drugs are used in each patient. No individualized medicine here! UAMS throws an intensive cocktail of every available anti-myeloma drug at each patient and hopes the therapy doesn’t kill them first!
Not my choice. But I am starting to see the wisdom of offering this option to low risk patients who are otherwise healthy enough to withstand the triple whammy of tandem auto transplants, sandwiched between waves and waves of every drug under the sun.
HEY! If it works, right?
The unfortunate reality for “experienced” myeloma patients is that definitive results that can be used to “win” these debates won’t be available for another ten years.
However, the good news is Dr. Durie and the IMF International Working Group are working on a way to speed-up the process by anticipating results long before they are achieved. Dr. Barlogie and his team at UAMS would argue they are already able to do this. Most others aren’t so sure.
That’s enough for today. Keep those comments coming! Have you been going back and reading comments your fellow readers have made following my posts the last few days? Lots of great ideas and questions!
By the way, I’m still looking for proof that keeping a positive attitude can help a cancer patient live longer. I haven’t forgotten that project. But there are just so many hours in the day…
Feel good and keep smiling! Pat
September 6th, 2012 at 3:49 pm
Decisions, decisions. My wife, Maria, started with standard Velcade/dex which, after five rounds, provided her with very nearly a complete response plus a load of neuropathy. Her doctor recommended an immediate transplant, but Maria held off so as not to preclude a long remission. Her disease, however, rebounded quickly, so she had only a five month drug-free interval until her transplant. The transplant held her disease at bay for over two and a half years, at which point she started full regime Revlimid plus 20 mg/wk dex. After one round she felt so poorly that the Rev frequency was reduced from every day to every second day. That worked for a year (until July 2012), at which point the every day frequency was restored. After one month, because her hemoglobin and neutrophils were going south, she was put on fifteen mg/day Rev while maintaining the twenty mg/wk dex. Someday, the onset of Rev resistance will put an end to this cat and mouse game, and she’ll heve to change the therapy. When that time comes she will have lots of choices among which are 1) return to full dex perhaps with an occasional transfusion (from experienve no EPO please)and perhaps along with a secondary drug (i.e. clarithromycin, vorinostat, or bendamustine, or 2) switch back to Velcade perhaps with a secondary (i.e. cyclophosphamide, panobinostat, perifosine, doxorubicin or romadepsin),3) expose one or the other of our great hopefuls pomalidomide and carlfilzomib to her disease and eventual resistance, or 4) enroll in a clinical trial if an appropriate one is available. With all the combinations and permutations, whatever she chooses to do will almost certainly be later shown to have been less than the best. This isn’t sent to elicit a response. I just wanted to unload. Pat, thanks for your postings. Charles
September 6th, 2012 at 5:43 pm
It isn’t fair, is it Charles? But at least most of us have options for a while. Please keep us updated on Maria’s progress!
September 6th, 2012 at 6:36 pm
Pat, I have gone through the UAMS program and the one thing that Barlogie has stated and Nick have mentioned is that if you can get into CR, and can maintain that CR for 3 years with maintenance therapy, that you have a 90% chance of “CURE”. So why not the way you are now attacking it, as long as you can reach this 3 year CR goal. I wonder if VRd induction with CR and 3 years of VRd maintenance with continued CR will one day provide the same results that UAMS is now achieving for the low risk patient without transplant. Wouldn’t that be great! We can dream can’t we!
Best Regards/Gary
September 6th, 2012 at 8:40 pm
Pat: That picture is not fair. I feel I have to justify the “frail” comment.
I was 69 when diagnosed with MM. After much research including visiting clinics and chatting with patients I selected Little Rock because of the spectacular results you shared on your web site. I was told I was not too old nor too frail.
The standard VTD-PACE (or kitchen sink) regime was thrown at me with my anticipation of a couple of transplants, three years maintenance and then clear sailing for 10 +years of water skiing. Unfortunately, frailty kicked in. Within a few days of administration I “acquired” pneumonia and ended up in the hospital. My prostate failed and I ended up with a urinary catheter. To top it all off I couldn’t harvest any stem cells….call it age or frailty.. or a need for a personalized treatment
Over the next year we tried valiantly to harvest stem cells and I finally have sufficient for a transplant. They are in the bank. Then, my MM markers increased and I spent 100 days of 2011 wandering the halls of UAMS. Here my frailties turned out to be my heart which could not tolerate carfilsomib or another combo of novel/conventional low dose chemo agents delivered metronomically. Finally, the drug Rituximab was “carefully”, administered in several six hour infusions despite scarey changes in my heart rate. It took me several months to recover. Thankfully it made my MM stable for a while. Unfortunately, it is getting to be treatment time again.
It is obvious that “standard” VTD-PACE will not work for me and I will never be on the curve in your blog. Like many other elderly I will be working around my “frailties” trying to find that combo of agents that will keep my disease in check for as long as possible.
Along the way I have learned about the importance of personalized treatment of patients including individualized dosing. I firmly believe that a VTD-PACE lite combo with dose levels determined with Pharmacokinetic profiles could have accommodated my frailties and perhaps put my my MM into remission. We will never know.
September 7th, 2012 at 12:28 am
Hi Gary! Fortunately or unfortunately, I was in CR for 3 years on just Rev/dex. Maybe if we would have hit it harder early? I understand that’s the theory…
September 7th, 2012 at 12:31 am
I’ve met Gary (comment #2) and he is far from frail. But his point is a good one. And I appreciated his concern for those of you/us that can’t undergo standard therapy for one reason or another. Thanks for caring and contributing, Gary!
September 7th, 2012 at 11:07 am
Thanks to Gary Blau for sharing his story. I too was sabotaged by frailities as I attempted a standard therapy regime at Mayo Scottsdale. Four months of CyBorD (cytoxan, velcade and dex) threw my heart into atrial fibrillation and caused my doctor to delay my stem cell transplant until I could get a leaky mitral valve (which may or may not have contributed to the atrial fibrillation) fixed. But I recently learned that repair of the mitral valve could leave an exposed plastic surface in my heart which would increase the risk of infection during a transplant. Checkmate! So, like Gary, I will rely on drugs to keep my disease in control as long as possible. I sometimes laugh that, as teenagers we were warned not to experiment with drugs, but as seniors that’s all we do!
September 7th, 2012 at 11:28 am
Funny! Al least you get to skip the transplant, Holt. Not a lot of fun…
September 7th, 2012 at 1:16 pm
Thanks for the silver lining Pat!
September 8th, 2012 at 9:05 pm
Hi, Pat–interesting to read your comments on your length of remission prior to SCT. I have not had a transplant and got a CR from the chemo. Last month marked 4 years that I was officially declared in remission. I just had my blood drawn and turned in my 24-hr. urine sample for testing yesterday and will get my results next Friday. It should be interesting to see how much longer the Revlimid will hold off the myeloma!
September 8th, 2012 at 9:30 pm
You don’t want to know, Susan! Four years is the median, I believe. I went four years and one month. Sounds like you are a lot luckier than I was! Keep us updated. Hope you get many more years of remission from your Rev. Dr. Durie told me about a patient of his from the original Revlimid study who is still in remission–almost ten years! See–you are only half way!
September 22nd, 2012 at 2:41 pm
Hi Pat,
I am new to your blog. It was strongly suggested at a Blood Cancer Support Group here in Fairview Park, OH. I was diagnosed 10/27/2010 with “smoldering” and have had my blood checked every 6 wks. I should also mention that I turned 64 this June. On Wednesday I had my 2nd bone marrow biopsy because my protein levels have been inching up and Revlmid has been suggested.
Here is the BIG question! I was also diagnosed with Diabetes that same week in October of 2010. No family record and I am thin! I have progressed from meds to meds plus insulin and am now insulin dependent! I’m wondering if there is a doctor out there somewhere who has been able to successfully treat these two together? Does that put me in the “high risk” category?
I’m enjoying your blog; especially on traveling tips. My children and grandchildren live in Seattle, Portland and Connecticut so I travel a lot.
Who else should I be posing this question to???
Thanks so much,
Jane
September 22nd, 2012 at 5:56 pm
Hi Jane! Lots of myeloma patients with diabetes. Any larger cancer clinic – with a hematology dept – should be able to handle your situation. Dexamethasone or prednisone can be a problem. Causes blood sugar spikes. But there is medication to control that. My advice? Call IMF Patient Hotline. Go to myeloma.org. Find “patient support” in red along the top. Drop down menu will include hotline. You give them your contact info, then someone calls you within 24 hrs. Excellent counselors that can easily point you in the right direction. Maybe you could email me and let me know what you find out so I could share it with my readers? Pat@HelpWithCancer.org. Thanks for reading! Good luck! Pat